The rate of oropharyngeal cancer (OPC) significantly increased among women and men from 1983 to 2002, almost exclusively in economically developed countries, according to a new study in the Journal of Clinical Oncology (November 18, 2013).
Researchers from the National Cancer Institute (NCI) found that rising OPC rates among men in economically developed countries were accompanied by fewer cases of both oral and lung cancers, two cancers strongly associated with smoking. In contrast, rising OPC rates among women were usually associated with higher numbers of oral and lung cancers.
Cancers of the oral cavity (OCC) and oropharynx are among the most common cancers worldwide, with an estimated 400,000 cases and 223,000 deaths in 2008, according to the study.
Tobacco and alcohol are strong risk factors for both OCC and OPC. In contrast, the association of human papillomavirus (HPV) is heterogeneous; HPV is an established cause of OPC (including the tonsil, base of the tongue, and other parts of the pharynx), but its etiologic role in OCC is unclear, the study authors noted.
Anil Chaturvedi, PhD, and his collaborators at the U.S. National Cancer Institute, Ohio State University, and the International Agency for Research on Cancer and the International Prevention Researcher Institute, both in Lyon, France, evaluated cancer registry data from more than 180,000 patients in 23 countries for the study.
The incidence of OCC has declined in recent years in most parts of the world, consistent with declines in tobacco use. In contrast, OPC incidence has increased during the last 20 years in several countries, including Australia, Canada, Denmark, the Netherlands, Norway, Sweden, the U.S., and the U.K.
These divergent incidence patterns for OCC and OPC led to the hypothesis that an exposure other than tobacco, perhaps HPV infection, was responsible for growing rates of OPC, the study authors pointed out. Consistent with this hypothesis, subsequent molecular studies in Australia, Sweden, and the U.S. reported dramatic increases in the proportion of HPV-positive OPCs since the 1980s, particularly among men and people younger than age 60.
"Understanding the burden of HPV-associated OPC worldwide could have important implications for prevention, potentially through prophylactic HPV vaccination, and could inform male vaccination policy," the researchers wrote.
Although characterized as a virus-related epidemic, given the predominantly country-specific nature of recent publications, it is unclear whether increasing OPC incidence overall, as well as in subgroups (specifically men), is a global phenomenon or is restricted to certain countries.
The researchers compared and contrasted incidence trends for OPC with those of OCC and lung squamous cell carcinomas to understand the impact of HPV vis-a-vis smoking on incidence patterns.
Among men, OPC incidence significantly increased in the U.S., Australia, Canada, Japan, and Slovakia, despite nonsignificant or significantly decreasing incidence of OCCs. In contrast, among women, in all countries with increasing OPC incidence (Denmark, Estonia, France, the Netherlands, Poland, Slovakia, Switzerland, and U.K.), there was a parallel increase in incidence of OCCs.
The increase in OPC among men was significantly higher at younger ages (younger than 60 years) than older ages in the U.S., Australia, Canada, Slovakia, Denmark, and U.K.
Results
Among men, the highest incidence rates of OPCs were observed in France, Slovakia, and Switzerland, whereas the highest rates of OCCs were observed in India, France, Slovakia, and Brazil. Among women, the rates were two to 17 times lower than the rates in men, with highest OPC incidence in Switzerland, France, and Denmark, and highest OCC incidence in India, the Philippines, and Denmark/France/Switzerland.
With the exception of Brazil, where incidence trends were nonsignificant, lung cancer incidence significantly declined in all other countries with significant increases in OPC incidence (U.S., Australia, Canada, Japan, Slovakia, Denmark, U.K, and the Netherlands).
Among women, significant increases in OPC incidence were observed exclusively in European countries (Denmark, Estonia, France, the Netherlands, Poland, Slovakia, Switzerland, and the U.K).
"Our observation of a potentially stronger role for HPV on increasing OPC incidence among men is supported by higher prevalence of HPV in oropharyngeal tumors among men compared with women in some geographic regions," the study authors found.
For example, the researchers pointed to a recent study of tumors collected by population-based cancer registries in the U.S. where HPV prevalence was significantly higher among men compared with women (Journal of Clinical Oncology, November 10, 2011, Vol. 29:32, pp. 4294-4301.
This male predominance is also supported by higher oral HPV prevalence among men than women in the U.S. general population, the researchers said.
An alternative explanation for increasing OCC (as well as OPC) incidence could be an increase in alcohol use among young people, which interacts with smoking to increase the risk of both OCC and OPC, the study authors noted. Likewise, the prevalence of chewing tobacco -- another strong risk factor for both OCC and OPC -- also could have increased among young people.
Conclusion
"Our observations of increasing OPC incidence in several countries around the world have important research and public health implications," the researchers concluded.
The reasons underlying a male predominance of HPV's potential role on observed incidence trends are currently unclear and need confirmation and further investigation, they noted.
"This male predominance also has important implications for male HPV vaccination policy in several countries," the researchers pointed out. "If proven efficacious, prophylactic HPV vaccines could be an effective primary prevention strategy for HPV-associated OPCs among men, particularly in countries with low vaccine coverage among women."
